Our primary goal is the effective design of a hemodialyzer based on microscale flow features that will enable portable, long-duration home dialysis, and not impose undue restrictions on patient activity. Our preliminary studies show that microchannel technology offers enhanced mass transfer and reduced dialysate use. These attributes will enable the delivery of a device for long-duration dialysis that more closely approaches normal kidney function. Our long-term objective is to develop a hemodialyzer appropriate for long duration portable or at home dialysis. The objectives of the proposed research is to understand and control variations in flow distribution and improve hemocompatibility of dialysis devices based on engineered microscale flow systems. By controlling these critical aspects of microscale devices, we will proceed with the fabrication and testing of a prototype portable dialysis system. Our specific aims are as follows: 1) Identify criteria for device fabrication that will lead to effective blood flow distribution within the device and 2) Identify criteria for blood contact surface modification that will lead to effective hemocompatibility, minimal bubble retention and no adverse effect on mass transfer within the device The work described here is innovative, as neither the application of engineered microchannels on both the blood and dialysate sides of a membrane, nor the simultaneous, directed modification of surface chemistry and microchannel geometry to achieve highly efficient hemodialysis, has been reported to date. Having identified the quantitative criteria consistent with effective blood flow distribution and hemocompatibility, we will have secured the remaining critical elements needed to support the fabrication and testing of a prototype portable dialysis system. Development of fully integrated, portable hemodialysis units will thus be enabled and the technology can be made available to the millions of people expected to require regular dialysis therapy in the years to come. The proposed research will be conducted by faculty and staff at Oregon State University's Microproducts Breakthrough Institute, the leading research organization in the U.S. focused on the miniaturization of transport-limited processes using microchannels. PUBLIC HEALTH RELEVANCE: While short-duration hemodialysis can deliver consistent and reproducible performance with minimal loss of essential blood constituents, frequent long-duration dialysis (8 hours every day) better simulates natural kidney function, and recent studies suggest that this approach significantly reduces the negative impacts of traditional short-duration dialysis treatment (Lindsay et al. 2003, Lockrigde et al 1999, Pierators, 1999). Ideally, long-duration dialysis could be practiced at home or in a portable, potentially wearable fashion. Such an option for the efficacious management of end stage renal disease is not currently feasible, as the necessary reduction in dialysis unit size must be accompanied by a substantial improvement in filtration efficiency, as current treatments require prohibitively high dialysate flow rates. The proposed research is focused on developing a dialysis unit with the characteristics appropriate for long- duration dialysis